The research outlined in the proposal is designed to provide a basic understanding of the role of defective herpes simplex viruses (HSV) in oncogenic transformation. It is proposed to use hamster embryo fibroblasts (HEF) obtained from the inbred LSH strain of Syrian hamsters to study transformation by (1) defective and UV-irradiated nondefective HSV, (2) defective and nondefective HSV DNA and (3) DNA fragments generated by mechanical shearing or E. coli Rl restriction endonuclease cleavage of defective and nondefective DNA. Quantitative transformation will be scored by colony formation in soft agar and by formation of foci of transformed cells on monolayers of HEF cells. Transformed cells will be tested for oncogenicity by injection into newborn Syrian hamsters. The presence of HSV-specific antigens in transformed cells will be determined by indirect immunofluorescence. DNA-RNA and DNA-DNA hybridization techniques will be used to determine the extent of viral gene expression and to quantitate the genetic complexity and genome equivalents present in transformed cultures. This proposed research will enable us to quantitate and to compare the transforming capacity of defective and nondefective herpes simplex virus in order to determine the relevance of defective HSV as potential oncogenic agents.